摘要
Although cellular sterol sensing and regulation of sterol biosynthesis are essential processes for eukaryotes,the mechanisms governing ergosterol homeostasis remain largely unknown in pathogenic fungi.In this study,we identify the transcription factor Ff SR as a key regulator of sterol homeostasis in Fusarium fujikuroi,the causative agent of rice bakanae disease worldwide.Deletion of Ff SR results in reduced ergosterol levels,increasing the susceptibility of F.fujikuroi to azole fungicides.Mechanistically,azole-induced ergosterol depletion promotes Ff SR phase separation,which facilitates its binding to cis-elements at target promoters,subsequently activating the expression of ergosterol biosynthesis genes.Conversely,when ergosterol levels are high,ergosterol binds to Ff SR,inhibiting its phase separation and transcriptional activation.Additionally,we identify a natural compound,natamycin,as a direct inhibitor of Ff SR,suppressing its phase separation and transcriptional capability.These findings highlight a novel mechanism by which fungal pathogens regulate ergosterol homeostasis through transcription factor phase separation,indicating that small molecules targeting Ff SR could serve as a synergist to enhance azole efficacy against pathogenic Fusarium.
基金
supported by the National Natural Science Foundation of China(U21A20219 and 31930088)
the National Key Research and Development Program of China(2022YFD1400100)
China Agriculture Research System(CARS-03-29)。
